Medical implants are used for a number of medical purposes, including the reinforcement of recently re-enlarged lumens, the replacement of ruptured vessels, and the treatment of disease such as vascular disease by local pharmacotherapy, i.e., delivering therapeutic drug doses to target tissues while minimizing systemic side effects. Such localized delivery of therapeutic agents has been proposed or achieved using medical implants which both support a lumen within a patient's body and place appropriate coatings containing absorbable therapeutic agents at the implant location.
The delivery of expandable stents is a specific example of a medical procedure that involves the deployment of coated implants. Expandable stents are tube-like medical devices, typically made from stainless steel, Tantalum, Platinum or Nitinol alloys, designed to be placed within the inner walls of a lumen within the body of a patient. These stents are typically maneuvered to a desired location within a lumen of the patient's body and then expanded to provide internal support for the lumen. The stents may be self-expanding or, alternatively, may require external forces to expand them, such as by inflating a balloon attached to the distal end of the stent delivery catheter.
Because of the direct contact of the stent with the inner walls of the lumen, stents have been coated with various compounds and therapeutic agents to enhance their effectiveness. These coatings may, among other things, be designed to facilitate the acceptance of the stent into its applied surroundings. Such coatings may also be designed to facilitate the delivery of one or more therapeutic agents to the target site for treating, preventing, or otherwise affecting the course of a disease or tissue or organ dysfunction. The coatings are typically on the order of 3 μm to 100 μm in thickness.
Where a stent is to be coated, care must be taken during its manufacture to ensure the coating is properly applied and firmly adherent to the stent. When the amount of coating is insufficient or is depleted through stripping of poorly adherent coating during manufacture or deployment within the patient's body, the implant's effectiveness may be compromised, and additional risks may be introduced. For example, when the coating of the implant includes a therapeutic, if some of the coating were removed during deployment, the therapeutic may no longer be able to be administered to the target site the desired manner. Similarly, if the therapeutic is ripped from the implant, it can reduce or slow down the blood flowing past it, thereby increasing the threat of thrombosis or, if it becomes dislodged, the risk of embolisms. In certain circumstances, the removal and reinsertion of the stent through a second medical procedure may be required where the coatings have been damaged or are defective.
The mechanical process of applying a coating onto a stent may be accomplished in a variety of ways, including, for example, spraying the coating substance onto the stent, so-called spin-dipping, i.e., dipping a spinning stent into a coating solution to achieve the desired coating, and electrohydrodynamic fluid deposition, i.e., applying an electrical potential difference between a coating fluid and a target to cause the coating fluid to be discharged from the dispensing point and drawn toward the target.
Common to these processes is the need to apply the coating such that the delivery rate can be predictably controlled. For example, in certain applications the goal may be the uniform delivery of the active substance while in other applications the desired effect would be a slow, sustained release of the active substance. Conventional methods include applying the active substance(s) in combination with a polymer to the surface of an implantable device. The drug is released as it elutes through the polymer material when it is placed in the body. One disadvantage of this method is that the polymer material and its composition control the drug's release rate. Another disadvantage is that the polymer provides only one release rate.
For example, the delivery of DNA or therapeutic agent can be inefficient, requiring large amounts of DNA and long delivery times for the stent to be an effective delivery system. This in turn can require large amounts of polymer coating on the stent, adapted to hold and release the DNA over the required period of time. However, if the coating is too thick, expansion of the stent can cause cracking of the coating, thus reducing the effectiveness of the coating. In addition, excessive coating may also cover the open areas in the stent, which normally allow passage of oxygen into the walls of the artery. On the other hand, if the coating is too thin, the entire supply of DNA or the therapeutic agent can be released within a short frame of time.
Controlled drug delivery from medical device coatings is desirable. As described, the conventional technologies rely on bulk release of therapeutic agents from carrier coatings. In this manner, often a rapid burst of the therapeutic agent occurs.